Loss of Genomic Diversity in a Neisseria meningitidis Clone Through a Colonization Bottleneck

Abstract

Neisseria meningitidis is the leading cause of epidemic meningitis in the “meningitis belt” of Africa, where clonal waves of colonization and disease are observed. Point mutations and horizontal gene exchange lead to constant diversification of meningococcal populations during clonal spread. Maintaining a high genomic diversity may be an evolutionary strategy of meningococci that increases chances of fixing occasionally new highly successful “fit genotypes”. We have performed a longitudinal study of meningococcal carriage and disease in northern Ghana by analyzing cerebrospinal fluid samples from all suspected meningitis cases and monitoring carriage of meningococci by twice yearly colonization surveys. In the framework of this study, we observed complete replacement of an A: sequence types (ST)-2859 clone by a W: ST-2881 clone. However, after a gap of 1 year, A: ST-2859 meningococci re-emerged both as colonizer and meningitis causing agent. Our whole genome sequencing analyses compared the A population isolated prior to the W colonization and disease wave with the re-emerging A meningococci. This analysis revealed expansion of one clone differing in only one nonsynonymous SNP from several isolates already present in the original A: ST-2859 population. The colonization bottleneck caused by the competing W meningococci thus resulted in a profound reduction in genomic diversity of the A meningococcal population.

Microevolution and Its Impact on Hypervirulence, Antimicrobial Resistance, and Vaccine Escape in Neisseria meningitidis

“…As in earlier studies, population bottlenecks and strong geographical signals are commonly observed. In one study, endemic MenA ST-2859 isolates (a member of cc5) were completely replaced by MenW ST-2881 isolates before reemerging as a highly clonal outbreak [161]. The authors suggest that competition with introduced MenW isolates caused a genetic bottleneck and that the reemerged ST-2859 clone may represent selection for a high-fitness variant of this lineage.…”